tbuckley/cabot-search huggingface dataset:
CARINA interim analysis: A non-interventional study of real-world treatment sequencing and outcomes in patients with advanced renal cell carcinoma initiated on first-line checkpoint inhibitor-based combination therapy.
Authors: Paul D. Nathan, Jennifer Allison, Natalie Charnley, Agnieszka Michael, Kathryn Moore, Anand Sharma, Bhupinder Klair, Valérie Perrot, James Larkin
Journal: Journal of Clinical Oncology (2023)

626 Background: First-line (1L) checkpoint inhibitor (CPI)-based combinations have become standard of care for patients with advanced renal cell carcinoma (aRCC). Data are required to inform optimal sequencing of aRCC therapies. CARINA is a non-interventional study of treatment sequencing and outcomes in patients with aRCC initiated on 1L CPI-based combination therapy. We report the results of a pre-planned interim analysis. Methods: We reviewed electronic prescribing records from participating UK specialist centers to identify patients (aged ≥ 18 years) with aRCC who received 2L therapy after 1L CPI-based combination therapy. The primary objective was to determine the treatment pathway for patients with aRCC who initiated treatment with a CPI-based combination and received subsequent therapy. Secondary objectives included treatment duration and objective response rate (ORR). Outcomes were evaluated for all patients (enrolled population [EP]) and for the patient subgroup who received 2L cabozantinib. Results: In total, 129 patients were eligible for inclusion in this interim analysis of the EP (mean [SD] age at diagnosis, 60.0 [9.9] years; 75.2% male; 77.3% clear-cell aRCC). Of these patients, 82.9% received 1L ipilimumab + nivolumab (Ipi + Nivo, n = 107) and 17.1% received axitinib + avelumab (Axi + Ave, n = 22); median (95% CI) duration of 1L treatment was 10.2 (9.1–17.1) weeks, ORR was 18.4%. The most commonly prescribed 2L therapies after Ipi + Nivo were cabozantinib (74.8%) and sunitinib (13.1%); the most commonly prescribed 2L therapies after Axi + Ave were lenvatinib + everolimus (45.5%) and cabozantinib (31.8%). Median (95% CI) duration of all 2L therapies was 23.6 (14.0–28.3) weeks, and median duration of 2L cabozantinib was 28.1 (20.1–37.1) weeks. ORR to 2L therapy was 30.4% for the EP, and 38.8% for the subgroup of patients who received 2L cabozantinib. Conclusions: In this interim analysis, the most commonly prescribed 2L therapies were cabozantinib and sunitinib after Ipi + Nivo, and lenvatinib + everolimus and cabozantinib after Axi + Ave. Antitumor response with 2L cabozantinib was observed after prior CPI-based therapy. Clinical trial information: NCT04957160 .
Adjuvant immunotherapy in renal cell carcinoma: A living systematic review and network meta-analysis (NMA).
Authors: Qurat Ul Ain Riaz Sipra, Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Huan He, Rabbia Siddiqi, Mahnoor Islam, Noureen Asghar, Waleed Ikram, Wenxin (Vincent) Xu, Parminder Singh, Thai Huu Ho, Mehmet Asim Bilen, Yousef Zakharia, Alan Haruo Bryce
Journal: Journal of Clinical Oncology (2023)

694 Background: The treatment landscape of localized renal cell carcinoma (RCC) is rapidly evolving. Recent trials have demonstrated contrasting efficacy with adjuvant immunotherapy. Therefore, we sought to assess the mixed treatment comparisons among different adjuvant treatment options using updated data from trials and quantified the absolute effect with these treatments stratified by risk categories. Methods: This living network meta-analysis was conducted using the living interactive evidence (LIvE) synthesis framework. We used stratified baseline risks of disease progression from observational data and at 5, 10, 15 years from the Leibovich risk stratification system (based on risk scores ranging from 0 to ≥15). Corresponding intervention risks were then approximated using relative effect estimates (from NMA) and baseline risks. The difference between CIRs and baseline risks were calculated to present absolute risk differences in each risk category. Results: This NMA included eight RCTs with 8480 participants and seven unique treatment options. Pembrolizumab (pembro; rank 1) was associated with improved disease-free survival (DFS) when compared to atezolizumab (atezo; rank 6; hazard ratio: 0.68; 0.49;0.93), and nivolumab-ipilimumab (nivoipi; rank 5; 0.68; 0.48-0.97). However, no statistically significant difference was observed between pembro and atezo for overall survival (0.53; 0.28-1.01). Survival data for nivoIpi was not reported. No new statistically significant differences were observed since last update. The absolute benefit of atezo and nivoipi was minimal with higher T and N patients (Table). The results were similar with increasing Leibovich risk scores. Conclusions: Current evidence favors the use of a risk adapted approach when offering adjuvant immunotherapy. Adjuvant pembrolizumab remains a preferred treatment in patients with RCC who underwent nephrectomy. [Table: see text]
Radiographic-pathologic concordance in the workup of locally radiorecurrent prostate cancer.
Authors: Luca Faustino Valle, Jeremie Calais, Leonard S. Marks, Steven Raman, Robert Evan Reiter, Matthew Rettig, John Shen, Johannes Czernin, Adam B Weiner, Michael L. Steinberg, Nicholas George Nickols, Albert J Chang, Paul Christopher Boutros, Huihui Ye, Masatoshi Hotta, Rong Rong Huang, Amar Upadhyaya Kishan
Journal: Journal of Clinical Oncology (2023)

313 Background: Advanced molecular PET/CT (mPET) studies are increasingly being utilized in conjunction with multiparametric MRI (mpMRI) to evaluate the burden of radiorecurrent disease in men who develop a biochemical recurrence following definitive radiotherapy (RT) for prostate cancer (PCa). However, radiographic concordance with pathologic confirmation of radiorecurrent disease in this setting is poorly described. We sought to conduct a patient-level analysis comparing concordance of radiographic and pathologic findings between mpMRI and mPET. Methods: Men who had previously undergone definitive RT for PCa and subsequently experienced treatment failure defined by the Phoenix definition were enrolled in a prospective registry study wherein radiographically identified local PCa recurrences were biopsied using mpMRI or mPET fusion (Artemis) with real-time ultrasound. Prior to biopsy, men underwent diagnostic imaging with mpMRI, advanced mPET ( 68 Ga-PSMA-11 or 18 F-FACBC), or both in order to identify a biopsy target. At least one imaging modality had to reveal a recurrent lesion based on PIRADS or PROMISE imaging classifications in order to prompt biopsy. Radiographic and pathologic findings were classified as either “treatment effect” or “recurrent disease”. Using biopsy as the reference standard, positive predictive value (PPV) was evaluated for mpMRI and mPET modalities separately. Results: Of 28 patients with radiographic recurrence on mpMRI or mPET, 10/28 (35.7%) exhibited treatment effect without evidence of active cancer on biopsy confirmation. Prostate adenocarcinoma was identified in 17/28 patient biopsies, whereas small cell prostate cancer was present in 1 patient. All 28 men underwent mpMRI prior to biopsy and 23/28 (82.1%) additionally underwent mPET; 19/23 (82.6%) underwent 68 Ga-PSMA-11 and 4/23 (17.4%) were imaged with 18 F-FACBC. Concordance in the assessment of recurrent disease between mpMRI and mPET was achieved in 12/23 (52.2%) men who underwent both imaging modalities. Among the 28 men who underwent mpMRI, PPV was 0.84, whereas PPV for the 23 men who underwent mPET was 0.70. Conclusions: In patients for whom clinical suspicion of radiorecurrence was high enough to warrant a biopsy, pre-biopsy mpMRI outperforms mPET in terms of PPV for detecting pathologically confirmed locally radiorecurrent PCa. Used in tandem, mpMRI and mPET might better select appropriate candidates for biopsy than either radiographic modality alone. While advanced mPET remains promising for detecting distant recurrences at the time of RT failure, biopsy confirmation following radiographic detection of local radiorecurrence remains essential for evaluating the true burden of local recurrence.
Gender disparities in the National Institutes of Health funding for genitourinary oncology.
Authors: Muhammad Zain Farooq, Sara Khan, Ibrahim Zahid, Aruba Sohail, Michael Vishal Jaglal
Journal: Journal of Clinical Oncology (2023)

264 Background: Traditionally, women are under-represented in academic fields and thus less likely to receive grants and funds. Here we assessed the National Institutes of Health (NIH) funding trend in allocation of R401 grants in Genito-urinary oncology (GU) stratified by gender. Methods: The data were retrieved from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditure) using GU-related search terms from 2018-2021. The gender was categorized using Genderize. The number of citations, publications, H-index, and seniority were obtained from Scopus and Web of Science in September 2022. Consumer Price Index was used to adjust funding amount to 2021 equivalent U.S. dollars. Linear regression was used for analysis. Results: A total of 873 NIH-funded R01 grants amounting to $388.5 million were awarded for GU research. Women (n= 206; 23.6% [95% CI: 20.8%-26.4%]) received fewer grants than men (n= 667; 76.4% [95% CI: 73.6%-79.2%]). Trending from 2018 to 2021, there was no significant difference in the number of grants awarded among both men (173 to 181, p=0.78) and women (50 to 53, p=0.92) within their groups. Similarly, there was no significant change in the grant amount (in millions) awarded among men (74.2 to 78.7, p=0.47) and women (23.6 to 22.4, p=0.30). Prostate cancer accounted for the greatest proportion of grants (n=689; 78.9% [95% CI: 76.2%-81.6%]), amounting to 304.4 million in 4 years. Of the 269 co-Principal Investigator (PIs), 240 (89.2% [95% CI: 85.5%-92.9%]) were men and 29 (10.8% [95% CI: 7.1%-14.5%]) were women. Male PIs compared to female PIs had a higher no. of publications (135 vs 106, p&lt;0.01). Funding amount was significantly associated with the number of publications (β=0.05; p&lt;0.01), seniority (β=0.10; p=0.015), institution (p&lt;0.01) and degrees (p=0.03). However, there was no significant association with gender (β=0.05; p=0.17). Conclusions: Our analysis shows continued gender disparity in R01 awards as only 1 in 5 grants were awarded to women during the fiscal years of 2018-2021. Thus, concerted efforts are required to bridge this gap and promote gender equity. [Table: see text]
The role of the size and number of index lesion in the diagnosis of clinically significant prostate cancer in patients with PI-RADS 4 lesions detected by multiparametric MRI of the prostate.
Authors: Mert Kılıç, Ersin Köseoğlu, Serdar Madendere, Metin Vural, Mevlana Derya Balbay, Tarik Esen
Journal: Journal of Clinical Oncology (2023)

44 Background: This study aimed to evaluate the contribution of the size and number of the sampled lesions to the diagnosis of clinically significant prostate cancer (CSPC) in patients who had PI-RADS 4 lesions detected by multiparametric MRI (mpMRI) of the prostate and underwent in-bore biopsy (IB). Methods: In this retrospective study, data of 295 patients who underwent IB for PI-RADS 4-5 lesions between 2012 and 2021 were analyzed, and a total of 159 patients with only PI-RADS 4 lesions were included. Clinical and radiological data, including age, PSA level, previous biopsy information, and the size and the number of PI-RADS 4 lesions were recorded. Patients with a lesion classified as Grade Group 2 and above were considered to have CSPC. Univariate and multivariate regression analyses were used to evaluate the factors affecting the diagnosis of prostate cancer (PCa) and CSPC. Results: A great majority (86.8%) of the patients had undergone a biopsy for the first time. About three-fourths (71.7%) of the patients had PCa, and half (54.1%) had CSPC. In multivariate analysis, the relationship between PCa and age, index lesion size, low PSA levels, and first biopsy patients were found significant, while CSPC exhibited a significant relationship with age and first biopsy patients. When the patients were divided into three groups according to the index lesion size (&lt;5 mm, 5-10 mm, and &gt;10 mm), the prevalence of PCa was 64.3%, 67.5%, and 82.4% and the prevalence of CSPC was 42.9%, 51.2%, and 64.7% respectively. Conclusions: While the size of PI-RADS 4 lesions was significant in predicting PCa, it had no significance in detecting CSPC. The number of lesions was insignificant in predicting both conditions. However, the prevalence of PCa was high, especially in patients with PI-RADS 4 lesions larger than 10 mm, which in turn increased the probability of the lesion being Grade Group 2 or above. [Table: see text]
Efficacy of immune-checkpoint inhibitor (ICI) combination as a first-line (1L) therapy in metastatic renal cell carcinoma (mRCC) with sarcomatoid histology: A systematic review and meta-analysis.
Authors: Rabbia Siddiqi, Gaurav Kumar, Hafsah Ijaz, Syed Arsalan Ahmed Naqvi, Ahsan Ayaz, Zaryab Bin Riaz, Alan Haruo Bryce, Thai Huu Ho, Irbaz Bin Riaz, Parminder Singh
Journal: Journal of Clinical Oncology (2023)

692 Background: Sarcomatoid mRCC exhibits poor prognosis and limited response to vascular endothelial growth factor pathway inhibition. Therefore, we assessed the efficacy of ICI combination therapy in this patient population using data from contemporary trials. Methods: MEDLINE and EMBASE were searched to identify phase III randomized controlled trials (RCTs) comparing the efficacy of ICI combinations with sunitinib monotherapy in patients with sarcomatoid mRCC. Patient important outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR). Precomputed hazard ratios (HR) with 95% confidence intervals (CI) for survival outcomes and binary outcome data for response rates (expressed as relative risk [RR] were meta-analyzed using a DerSimonian-Lairds random-effects method. Mixed treatment comparisons among different ICI combinations were made using a network-meta-analysis within the Bayesian framework. The surface under the cumulative ranking curves (SUCRA) were computed to assess the relative treatment rankings. Results: Six RCTs with a total of 618 patients were considered eligible for inclusion. ICI combination therapy was significantly associated with improved OS (HR: 0.56; 95% CI: 0.43-0.72) and PFS (HR: 0.50; 0.40-0.62), increased ORR (RR: 2.42; 1.92-3.06), and CR (RR: 4.23; 2.00-8.93) when compared to sunitinib in patients with sarcomatoid mRCC (Table). The results were consistent with Hartung-Knapp adjustment. Mixed treatment comparisons using current data revealed no statistically significant differences among different ICI combinations. However, the combination of nivolumab-ipilimumab was consistently ranked higher (rank 2 for OS, ORR, and CR) and may potentially be more efficacious than other counterparts. Conclusions: Current evidence suggests improved survival, delayed disease progression and increased response rates with the use of ICI combination therapy in patients with sarcomatoid mRCC. [Table: see text]
Cost-effectiveness of abiraterone acetate for high-risk nnon-metastatic prostate cancer.
Authors: Nataniel Hernan Lester-Coll, Shahid Sattar Ahmed, H. James Wallace, Brian L. Sprague, Steven Ades
Journal: Journal of Clinical Oncology (2023)

358 Background: In a primary analysis of the STAMPEDE protocol, the addition of Abiraterone acetate to androgen deprivation therapy (ADT) in men with castration sensitive, high-risk, non-metastatic prostate cancer was associated with significantly higher rates of metastasis-free survival compared with ADT alone. However, the cost-effectiveness of Abiraterone in this population remains unaddressed. Methods: A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) associated with ADT with or without Abiraterone. This analysis was performed from a United States healthcare sector perspective. We estimated drug acquisition costs using the Federal Supply Schedule. Given current heterogeneity in prescription drug coverage, we used both brand-name and generic drug prices. The willingness-to-pay (WTP) threshold was $100,000 per QALY. Analyses were performed over the published STAMPEDE trial with median follow-up duration of 72 months. Model input parameters were based on the STAMPEDE trial data as well as best available and most recent data provided in the published literature. Sensitivity analyses explored uncertainty with regard to the model assumptions. Results: Using brand-name pricing, the addition of Abiraterone to ADT was associated with an increase in net costs by $217,616, and an increase in QALYS by 0.79. Therefore, the ICER associated with brand-name Abiraterone was $277,156 per QALY. Sensitivity analyses revealed that the monthly price of Abiraterone would need to be less than or equal to $2,581 in order to be cost-effective at a WTP threshold of $100,000 per QALY. In contrast, generic Abiraterone was associated with an increase in net costs by $45,325, and a cost-effective ICER of $57,726 per QALY. Conclusions: Abiraterone for high-risk non-metastatic prostate cancer is cost-effective using generic pricing. However, current brand-name pricing is roughly four times the threshold of cost-effectiveness, underscoring the need to increase access to generic drugs in the United States.
Associations of <i>TACSTD2</i>/TROP2 and <i>NECTIN-4</i>/NECTIN-4 with molecular subtypes, PD-L1 expression and <i>FGFR3 </i>mutational status in two advanced urothelial bladder cancer cohorts.
Authors: Veronika Bahlinger, Annalena Branz, Pamela Strissel, Reiner Strick, Fabienne Lange, Carol-Immanuel Geppert, Niklas Klümper, Michael Hölzel, Sven Wach, Helge Taubert, Danijel Sikic, Bernd Wullich, Miriam Angeloni, Fulvia Ferrazzi, Lauri Diehl, Maria Kovalenko, Emon Elboudwarej, Juliane Margarete Juergensmeier, Arndt Hartmann, Markus Eckstein
Journal: Journal of Clinical Oncology (2023)

554 Background: Treatment options for advanced urothelial carcinoma (aUC) rapidly evolved in recent years. Besides immunomodulative therapeutic options like anti-PD-(L)1 inhibitors and inhibitors targeting FGFR alterations, two new antibody-drug conjugates (ADC), sacituzumab govitecan (SG) and enfortumab vedotin (EV), have been approved for treatment. However, little is known about associations of specific aUC properties and the surface target expression of TROP2 and NECTIN-4. This study characterizes associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 gene and protein expression with morphomolecular and clinico-pathological characteristics of aUC in two large independent cohorts. Methods: The TCGA BLCA (n=405) and the CCC-EMN (n=247) cohorts were retrospectively analyzed. Expression of mRNA and protein for TACSTD2/TROP2 and NECTIN-4/NECTIN-4 was measured and correlated with clinico-pathological characteristics, molecular subtypes, FGFR3 alterations and PD-L1 expression. Results: TACSTD2/TROP2 and NECTIN-4/NECTIN-4are highly expressed at protein and transcript level in aUC, and their expression status did not correlate with patient survival in two independent cohorts. NECTIN-4/NECTIN-4 expression was higher in luminal tumors and reduced in squamous aUCs. NECTIN-4 was negative in 10.6% of samples, and 18.4% of samples had low expression (H-Score &lt; 15). TROP2 negativity rate amounted to 6.5%. TACSTD2 and NECTIN-4 expression was reduced in neuroendocrine-like and/or protein-based double negative tumors. TROP2 and NECTIN-4 negative tumors (protein level) included one sarcomatoid and four neuroendocrine aUC. FGFR3 alterations and PD-L1 expression on tumor and immune cells did not associate with TROP2 or NECTIN-4 expression. Conclusions: TACSTD2/TROP2 and NECTIN-4/NECTIN-4 are widely expressed in aUC, independent of FGFR3 alterations or PD-L1 expression. Expression loss is associated with aggressive morphomolecular aUC subtypes, i.e. neuroendocrine(-like) and sarcomatoid aUC. TROP2 and NECTIN-4 are widely expressed in aUC thus representing suitable targets for novel ADC treatment for the majority of aUC patients.
Association of plasma vitamin D with outcomes in patients with germ cell tumour.
Authors: Peter Lesko, Barbora Vlkova, Katarina Kalavska, Valentina De Angelis, Jana Obertova, Zuzana Orszaghova, Patrik Palacka, Katarina Rejlekova, Zuzana Sycova-Mila, Jozef Mardiak, Michal Chovanec, Peter Celec, Vera Miskovska, Michal Mego
Journal: Journal of Clinical Oncology (2023)

429 Background: Testicular cancer is the most common malignancy among young men. Vitamin D has pluripotent effects on cancer pathogenesis and plays a role in the metastatic cascade. The aim of this study is to analyze plasma vitamin D in association with clinico-pathological findings and prognosis in patients with testicular germ-cell tumours (GCTs). Methods: This study included 120 newly diagnosed and/or relapsed GCTs patients treated from April 2013 to July 2020. Blood samples were drawn at the time before 1 st chemotherapy cycle as well as before the 2 nd cycle. Plasma vitamin D was measured using ELISA and matched with disease characteristics and correlated with the patient outcome. For survival analysis the cohort was dichotomized to “low” and “high” based on median vitamin D. Results: Mean ± standard error of mean plasma vitamin D in GCTs patients was 15.87±0.68 mg/ml. Patients with brain metastases had significantly lower D vitamin compared to patients without brain metastases (10.9 ± 3.05 vs 15.99 ± 0.7, p=0.034). Vitamin D was not associated with other patient characteristics. Low vitamin D was associated with an unfavorable response compared to favorable responses (11.26 ± 1.84 vs 16.47± 0.74, p=0.016), with disease recurrence (16.19 vs 13.71, p=0.011) and with inferior progression-free survival but not with overall survival (HR= 3.02, 95%CI (1.36-6.71), p=0.014 for PFS and HR= 2.06, 95%CI (0.84 – 5.06), p=0.135 for OS, respectively). Conclusions: Our study suggests a prognostic value of pretreatment vitamin D concentrations in GCTs patients. Low plasma vitamin D was associated with unfavorable response to therapy and disease recurrence. However, it remains to elucidated whether the biology of the disease confirms a causative role of low vitamin D and if its supplementation affects the outcome.